Effects of forskolin and cyclic nucleotides in animal models predictive of antidepressant activity: interactions with rolipram.

摘要: Forskolin, a direct activator of the catalytic subunit adenylate cyclase (AC), and cyclic nucleotide analogs dibutyryl cAMP (dBcAMP), 8-bromo (8-BrcAMP) cGMP (dBcGMP) were tested for their ability to reverse hypothermia or hypokinesia mice depleted presynaptic endogenous monoamines by pretreatment with reserpine, α-methyl-p-tyrosine p-chlorophenylalanine. Forskolin decreased rectal temperature inhibited locomotor activity in normal mice. In brain forskolin reversed hypokinesia; dBcAMP 8-BrcAMP antagonized but only marginally effective reversing hypokinesia. DBcGMP was inactive. The antihypothermic action salbutamol enhanced novel antidepressant selective phosphodiesterase inhibitor rolipram (4RS-[3-cyclopentyloxy-4-methoxy-phenyl]-2-pyrrolidone). As an indirect effect via release stimulating postsynaptic receptors precluded monoamine-depleting pretreatment, are thought exert directly increasing availability. This is achieved activation AC substitution cAMP. These findings suggest that crucially linked availability within effector cells. successful treatment endogenously depressed patients supports this assumption.